The goal of this industry/academic research is to develop multivalent vaccines for prevention and treatment of breast cancer. Towards this goal, one aim of this phase 1 research is to identify novel breast tissue specific sequences that are frequently over expressed in human breast tumors. Such sequences would be expected to be candidate breast tumor antigens. The second aim is to identify novel HLA-A2 binding immunogenic peptides from breast tumor antigens and study their immunogenicity as multivalent vaccines. Towards these aims, we propose to develop a panel of human breast tissue specific cDNAs and use them as probes to screen Northern blots of RNAs from human breast tumors and normal human breast tissue. Those cDNAs that are frequently over expressed in breast tumors will be considered to encode candidate breast tumor antigens and will be isolated as full length molecules. These cDNAs will also be tested for expression of the encoded protein and then used for development of specific monoclonal antibodies. The breast tumor antigen-encoding cDNAs will then be evaluated for the presence of HLA-A2 binding peptides which will be subsequently used for development and testing of multivalent vaccines. The materials developed in this Phase I research will have application in Phase I and Phase II clinical trials to be proposed in the Phase II of this research. PROPOSED COMMERCIAL APPLICATIONS: Peptide and cDNA vaccines developed in this Phase I research are directly applicable for use in Phase I and II clinical trials to be proposed in Phase II of this research. If encouraging results are obtained, these vaccines will be tested in a multi center randomized study to evaluate their efficacy in breast cancer prevention in women at high risk for developing this cancer. There are 29 million women in U.S. alone who are at high risk for developing breast cancer, and this suggests a huge potential for commercial application.